Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients.

S-1 is an oral fluoropyrimidine anti-neoplastic agent that is converted by CYP2A6 to 5-fluorouracil (5FU). We prospectively studied the pharmacokinetics and pharmacodynamics of S-1 in two groups of East Asian and Caucasian patients with solid malignancy refractory to standard chemotherapy, or for which 5FU was indicated, to elucidate differences in relation to CYP2A6 genotype and phenotype. S-1 was given orally at 30 mg/m(2) b.i.d. for 14 days every 21 days. Dose normalized AUC(0-48 h) for tegafur (P = 0.05) and gimeracil (P = 0.036) were higher in East Asians; conversely, AUC(0-48 h) of fluoro-ß-alanine was higher in Caucasians (P = 0.044). Exposure to 5FU was similar in both groups (P = 0.967). Mean cotinine:nicotine ratio was 54% higher in the Caucasian group (P = 0.03), and correlated with oral clearance of tegafur (r = 0.59; P = 0.002). Grade 3/4 gastrointestinal toxicities were more common in Caucasians than Asians (21%vs 0%). Treatment with S-1 yields no significant difference in 5FU exposure between Caucasians and East Asians.

Long term survival on S-1 monotherapy in a patient with recurrent stage IV pancreatic cancer.

CONTEXT: Pancreatic cancer is the third most common gastrointestinal malignancy in the United States. Due to difficulty in diagnosis, 40% of patients are stage IV by the time of diagnosis and median survival is only four to six months. Current therapy for advanced pancreatic cancer focuses largely on gemcitabine. However, a relatively new drug, S-1, is showing promising results. Phase II studies of S-1 monotherapy and recent combination with gemcitabine were conducted for the treatment of metastatic pancreatic cancer. The early phase II study demonstrated a response rate approaching 20% while the combination is reaching more than 35%. CASE REPORT: We report a 68-year-old man who presented with stage IIB pancreatic cancer which advanced to stage IV after undergoing a Whipple procedure and adjuvant treatment with gemcitabine. The patient was refractory to treatment with gemcitabine as well as irinotecan, taxotere, and cetuximab. He subsequently participated in a trial involving the drug S-1. He achieved 10-month survival with preserved quality of life: he had 14 cycles of S-1 and maintained an ECOG performance status of 0-1 throughout. CONCLUSION: For this patient, 14 cycles of S-1 were well-tolerated for 10 months after failing two prior chemotherapeutic regimens suggesting important insight that S-1 may be active and convenient for its oral use and it may have favorable safety profile in patients with metastatic pancreatic cancer. Randomized trials are warranted to determine the effectiveness of S-1 for the treatment of pancreatic cancer.